Package components for radiochemical sterilization

ABSTRACT

This invention deals with package components for radiochemical sterilization of medical or pharmaceutical products consisting of a hermetically sealed foil pack containing (1) a solid device, as in absorbable sutures and meshes, in a perforated holder or a liquid formulation in a sealed, flexible dispenser, as in absorbable cyanoacrylate-based tissue adhesive; (2) a microparticulate, unstabilized polyformaldehyde as a source of radiolytically generated formaldehyde encased in a sealed pouch comprising a porous, non-woven or woven fabric; and (3) a nitrogenous compound capable of reacting with residual formaldehyde, such as melamine or urea, that is encased in a sealed pouch comprising a porous, non-woven or woven fabric.

FIELD OF THE INVENTION

This invention relates to specially tailored package components forradiochemically sterilized (RC-Sd) medical devices in a hermeticallysealed foil pack using a combination of low-dose, high-energy radiationand radiolytically generated gaseous formaldehyde, wherein saidcomponents include a solid polymeric source of formaldehyde in a porouscarrier, a perforated device holder, and a solid reactive absorbent toremove residual formaldehyde.

BACKGROUND OF THE INVENTION

Radiochemical sterilization (RC-S) was first disclosed by this inventorin U.S. Pat. No. 5,422,068 and frequently described as the first novelapproach to medical device sterilization since the early use of chemicalsterilization in the presence of formaldehyde or ethylene oxide (Et-O)and high-energy radiation in the presence of gamma radiation or electronbeam. It provides the medical device industry with a unique, hybridprocess encompassing the attributes of chemical and radiationsterilization (RS) without the drawbacks associated with the use of theparent processes. Limitations on use of the most commonly used methods(namely, traditional RS and Et-O) have grown in the past three decadesbecause of (1) degradation or undesirable changes in the properties ofcertain polymeric devices, such as those made from absorbable polyestersand polypropylene, caused by gamma radiation; (2) ineffectivesterilization of simple and complex devices with Et-O and associateddevice recalls; and (3) toxic and explosive nature of Et-O. In contrast,the RC-S method combines the attributes of chemical sterilants andhigh-energy radiation and it entails (1) terminal sterilization ofdevices in a hermetically sealed package; (2) use of precisely generatedformaldehyde through controlled radiolytic (caused by controlling themass of the formaldehyde precursor and radiation dose) degradation of asolid polyformaldehyde insert to achieve surface sterility; and (3) lessthan 40% of the traditional radiation dose can be used to achievesurface and bulk device sterility—the radiation penetrates the mass ofthe device to ensure bulk sterility while complementing the formaldehydein securing surface sterility. The commercial application of RC-S tosegments of the medical device industry based on absorbable polyesterswill represent a major milestone in such a fast-growing fieldencompassing traditional and new surgical products and innovativeconstructs for tissue engineering. A logical extension of the RC-Sapplication will be for polypropylene-based devices, such as sutures,syringes, and many types of diagnostic devices.

The first commercial application of this technology will be radiationsterilization of absorbable polymeric devices. The use of RC-S isexpected to extend to (1) other radiation-sensitive, biostable devices,such as those made of polypropylene (e.g., sutures and syringes); and(2) multicomponent packages, including resterilizable surgical kitscontaining both absorbable and non-absorbable components. However, U.S.Pat. No. 5,422,068 failed to address certain package-relatedrequirements for the successful commercial use of the RC-S technology,which include (1) using a specially prepackaged, solid polymericprecursor that allows maximum diffusion of the generated formaldehydeinto the gaseous environment without hindering its fugacity; (2) using aspecially designed device holder for insuring the free diffusion of thegenerated formaldehyde from its precursor to effectively interact withany microflora on the medical device surface; and (3) providing amechanism for practically irreversible, gradual immobilization of theresidual formaldehyde in the package shortly after inactivating anymicroflora about the device. And this provided the incentive to explorethe use of the package components subject of this invention that permitmeeting the three requirements noted above.

SUMMARY OF THE INVENTION

This invention deals with package components for radiochemicalsterilization of medical and pharmaceutical products. In particular,this invention deals with a hermetically sealed package for use inradiochemical sterilization of at least one medical device thereincomprising an essentially gas impervious, moisture impervious sealedouter sheet, preferably of laminated foil, a perforated folder forholding the individual device contained within the sealed outer sheet, aradiolytically depolymerizable microparticulate polyformaldehyde encasedand retained in a first sealed porous pouch contained within the sealedouter sheet and a formaldehyde-reactive microparticulate compoundencased and retained in a second sealed porous pouch contained withinthe sealed outer sheet. The radiochemical sterilization is achieve inthe presence of (1) high energy radiation at a dose of less than 10 kGy,wherein said radiation comprises gamma rays or electron beam, or (2)high energy radiation at a dose of less than 5 MeV of X-rays.

Another general aspect of this invention addresses a hermetically sealedpackage for use in radiochemical sterilization of at least one medicaldevice therein comprising an essentially gas impervious, moistureimpervious sealed outer sheet, a perforated folder for holding theindividual device contained within the sealed outer sheet, aradiolytically depolymerizable microparticulate polyformaldehyde encasedand retained in a first sealed porous pouch and a formaldehyde-reactivemicroparticulate compound encased and retained in a second sealed porouspouch, wherein (1) the perforated folder for holding the individualdevice is made of dried cellulosic material or polyolefin such aspolyethylene; (2) the radiolytically depolymerizable polyformaldehydemicroparticulate comprises unstabilized polyformaldehyde; (3) theformaldehyde reactive microparticulate compound comprises a reactivenitrogenous compound, capable of reacting with gaseous formaldehyde,selected from the group represented by urea and melamine; and (4) theporous pouch for encasing the polyformaldehyde or theformaldehyde-reactive compound is a non-woven fabric construct andpreferably comprising a polyolefinic material selected from the grouprepresented by polyethylene, polypropylene, and ethylene/propylenecopolymer, alternatively, the pouch is made of a woven fabric constructmade of polyethylene terephthalate.

In terms of application, this invention relates to a hermeticallysealed, preferably laminated foil pack for use in radiochemicalsterilization of at least one medical device therein comprising aperforated folder for holding the individual device, a radiolyticallydepolymerizable microparticulate polyformaldehyde encased and retainedin a sealed porous pouch and a formaldehyde-reactive microparticulatecompound encased and retained in a sealed porous pouch, wherein thedevice comprises an absorbable suture braid, an absorbable monofilamentsuture, an absorbable mesh, a partially absorbable vascular graft, anabsorbable device for internal bone fixation, an absorbable stent, ametallic stent with an absorbable fibrous construct, and any vascularrepair device comprising at least one absorbable component.Alternatively, the device comprises a medical device comprisingpolypropylene, as in monofilament polypropylene sutures.

A key aspect of this invention deals with a hermetically sealedpreferably laminated foil pack for use in radiochemical sterilization ofa least one medical device therein containing a radiolyticallydepolymerizable polyformaldehyde microparticulate encased and retainedin a sealed porous pouch made of non-woven polyolefin or a wovenpolyethylene terephthalate, and a formaldehyde reactive microparticulatecompound encased and retained in a sealed porous pouch similar to thatused for the polyformaldehyde, wherein the radiochemical sterilizationis achieved in the presence of (1) high energy radiation at a dose ofless than 10 kGy, wherein said radiation comprises gamma rays orelectron beam or (2) high energy radiation at a dose of less than 5 MeVof X-rays.

Another key aspect of this invention addresses a hermetically sealedpreferably laminated foil pack for use in radiochemical sterilization ofa least one medical device therein and said foil pack containing (1) aradiolytically depolymerizable polyformaldehyde microparticulate encasedand retained in a sealed porous pouch made of a non-woven polyolefin ora woven polyester; (2) a formaldehyde reactive microparticulate compoundencased and retained in a sealed porous pouch similar to that used forthe polyformaldehyde; and (3) a medical device comprising a flexiblesealed polymeric dispenser that is preferably made of a polyolefin, suchas polyethylene and polypropylene containing a cyanoacrylate-basedtissue adhesive. It is preferred that the cyanoacrylate-based tissueadhesive comprising methoxypropyl cyanoacrylate is contained in a sealedtapered flexible tube made of polyethylene or polypropylene.Alternatively, the tissue adhesive is contained in a sealed or tightlyclosed glass container. It is also preferred that the sealed laminatedfoil pack is further comprising a formaldehyde reactive nitrogenouscompound, capable of reacting with gaseous formaldehyde, selected fromthe group represented by urea and melamine encased and retained in asealed non-woven polyolefin or woven polyethylene terephthalate porouspouch.

A key aspect of this invention deals with a hermetically sealedpreferably laminated foil pack for use in radiochemical sterilization ofat least one medical device wherein the medical device comprises aflexible sealed polymeric dispenser containing a cyanoacrylate-basedtissue adhesive. The sealed pack also contains unstabilizedmicroparticulates of radiolytically depolymerizable polyformaldehydeencased and retained in a sealed non-woven polyolefin or a wovenpolyethylene terephthalate porous pouch.

BRIEF DESCRIPTION OF THE FIGURES OF THE DRAWING

The accompanying drawings, which are incorporated in and constitute apart of the specification, illustrate presently preferred embodiments ofthe present invention and, together with the general description givenabove and the detailed description of the preferred embodiments givenbelow, serve to explain the principles of the present invention.

FIG. 1 is a top view of the perforated folder in accordance with thepresent invention in its unfolded configuration;

FIGS. 2-4 illustrate the folder of FIG. 1 as it is being folded; and

FIG. 5 shows the perforated folder of Figure in its folded and securedconfiguration.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Radiochemical sterilization (RC-S) disclosed in U.S. Pat. No. 5,422,068is, for the most part, based on the combined use of low-dose,high-energy radiation and radiolytically generated formaldehyde.However, successful practical application of the RC-S unique technologyfor sterilization of biomedical and pharmaceutical devices imposes otherequally unique technological challenges that needed to be addressed. Andthis invention deals with practical and effective solutions to thesechallenges. The first among these challenges relates to the need to usea minimum amount of the formaldehyde precursor and its housing in asecure reservoir that will allow the radiolytically generatedformaldehyde to escape freely to the gaseous environment and remainactive for the desired period of time about the device to be sterilized.For this, the present invention calls for (1) the use of a highlyradiolabile form of polyformaldehyde such as that known in the trade asunstabilized Celcon® M-90; (2) microparticulate solid polyformaldehydewith exceptionally high surface-to-volume ratio to allow the gaseousformaldehyde to escape freely into the gaseous environment in thepackage and about the device; (3) a hermetically sealed gas and moistureimpervious, preferably foil, pack filled with dry, essentially inertgas, such as nitrogen or argon—this is to maintain the formaldehydeactivity by eliminating its partitioning with traces of water or partialoxidation; (4) incasing the solid polyformaldehyde in a sealed,non-woven, porous fabric pouch (preferably made of Tyvek®) or woven,porous fabric pouch (preferably made of polyethylene terephthalate) thatretain the solid but allow the formaldehyde to escape freely to theenvironment about the device; (5) a holder of the device that allows theformaldehyde to circulate freely about the device—for this, a holder, asin the case of a folder for surgical suture, is described in thisinvention as depicted in FIGS. 1-5 to have perforated walls wherein saidfolder can be made of a flexible polymer, such as polyethylene (orpolypropylene) or dried cellulosic paper (this can also act as adesiccant); and (6) a packaging system that is impermeable to gases,such as formaldehyde—this is a laminated foil used in this invention toproduce the hermetically sealed primary package for devices that areheld in folders or secondary packages for prepackaged liquid tissueadhesive contained in sealed, flexible polymeric dispensers. The sealedpackage may also comprise a traditional desiccant, such as anhydroussilica or molecular sieve, contained in a permeable solid carrier. Thesecond challenging area relates to minimizing or eliminating residualformaldehyde in the gaseous environment of the package shortly afterdeactivating any micro-organisms which may be present within thepackage. For this, the present invention discloses (1) a limited mass ofthe Celcon® M-90 to generate a sufficient, but not excessive, amount ofgaseous formaldehyde to achieve sterility; (2) the surprising ability ofCelcon® M-90 microparticulates to absorb part of the gaseousformaldehyde which subsequently polymerizes and becomes part of thesolid precursor; and (3) the use of chemical compounds that have anexceptional propensity for reacting with free and accessible gaseousformaldehyde leading to its practical elimination from the gaseousenvironment about the device—for this, reactive nitrogenous compounds,such as melamine and urea, are encased in sealed porous pouches (similarto those used to house polyformaldehyde) and placed as package insertsin the primary package or secondary package for sutures/meshes, orliquid tissue adhesives, respectively.

A key aspect of this invention is the judicious selection of thearticles to sterilize and focusing on those which cannot be effectivelysterilized by other, more traditional means. Accordingly, this inventiondeals with the RC-S of (1) absorbable polyester-based sutures; (2) fullyor partially absorbable fibrous vascular grafts; (3) fully or partiallyabsorbable meshes for use in repairing tissue defects; and (4) fully orpartially absorbable scaffolds for use in tissue engineering, or toallow natural tissue ingrowth. Obviously, all these forms of devices areknown to degrade upon using the traditional radiation sterilization (RS)(at a nominal dose which may approach or exceed 25 kGy) or cannot beeasily and effectively sterilized using ethylene oxide because of thecomplex geometries and associated problems of gas accessibility toachieve sterility and removal of residual toxic gases at the conclusionof the sterilization process.

Another key aspect of this invention deals with unique use of RC-S tosterilize cyanoacrylate-based tissue adhesive. These are known toundergo unwanted level of radiation-induced polymerization when thetraditional radiation sterilization cycle of 25 kGy is used. When usingRC-S, the liquid cyanoacrylate-based tissue adhesive is filled in aflexible dispenser (typically made of polyethylene or polypropylene)that is sealed under nitrogen and then placed in the new, hermeticallysealed laminated foil pack described in this invention, as the secondarypackage.

This invention deals generally with a hermetically sealed, laminatedfoil pack for use in radiochemical sterilization of at least one medicaldevice therein comprising a perforated folder for holding the individualdevice, a radiolytically depolymerizable microparticulatepolyformaldehyde encased and retained in a sealed porous pouch and aformaldehyde-reactive microparticulate compound encased and retained ina sealed porous pouch, wherein the radiochemical sterilization isachieve in the presence of (1) high energy radiation at a dose of lessthan 10 kGy, wherein said radiation comprises gamma rays or electronbeam, or (2) high energy radiation at a dose of less than 5 MeV ofX-rays.

Another general aspect of this invention addresses a hermeticallysealed, laminated foil pack for use in radiochemical sterilization of atleast one medical device therein comprising a perforated folder forholding the individual device, a radiolytically depolymerizablemicroparticulate polyformaldehyde encased and retained in a sealedporous pouch and a formaldehyde-reactive microparticulate compoundencased and retained in a sealed porous pouch, wherein (1) theperforated folder for holding the individual device is made of driedcellulosic material or polyolefin such as polyethylene; (2) theradiolytically depolymerizable polyformaldehyde microparticulatecomprises unstabilized polyformaldehyde; (3) the formaldehyde reactivemicroparticulate compound comprises a reactive nitrogenous compound,capable of reacting with gaseous formaldehyde, selected from the grouprepresented by urea and melamine; and (4) the porous pouch for encasingthe polyformaldehyde or the formaldehyde-reactive compound is anon-woven fabric construct and preferably comprising a polyolefinicmaterial selected from the group represented by polyethylene,polypropylene, and ethylene/propylene copolymer, alternatively, thepouch is made of a woven fabric construct made of polyethyleneterephthalate.

In terms of application, this invention relates to a hermeticallysealed, laminated foil pack for use in radiochemical sterilization of atleast one medical device therein comprising a perforated folder forholding the individual device, a radiolytically depolymerizablemicroparticulate polyformaldehyde encased and retained in a sealedporous pouch and a formaldehyde-reactive microparticulate compoundencased and retained in a sealed porous pouch, wherein the devicecomprises an absorbable suture braid, an absorbable monofilament suture,an absorbable mesh, a partially absorbable vascular graft, an absorbabledevice for internal bone fixation, and an absorbable stent.Alternatively, the device comprises a medical device comprisingpolypropylene, as in monofilament polypropylene sutures.

A key aspect of this invention deals with a hermetically sealedlaminated foil pack for use in radiochemical sterilization of a leastone medical device therein comprising a radiolytically depolymerizablepolyformaldehyde microparticulate encased and retained in a sealedporous pouch made of non-woven polyolefin or a woven polyethyleneterephthalate, and a formaldehyde reactive microparticulate compoundencased and retained in a sealed porous pouch similar to that used forthe polyformaldehyde, wherein the radiochemical sterilization isachieved in the presence of (1) high energy radiation at a dose of lessthan 10 kGy, wherein said radiation comprises gamma rays or electronbeam or (2) high energy radiation at a dose of less than 5 MeV ofX-rays.

Another key aspect of this invention addresses a hermetically sealedlaminated foil pack for use in radiochemical sterilization of a leastone medical device therein and said foil pack comprising (1) aradiolytically depolymerizable polyformaldehyde microparticulate encasedand retained in a sealed porous pouch made of a non-woven polyolefin ora woven polyester; (2) a formaldehyde reactive microparticulate compoundencased and retained in a sealed porous pouch similar to that used forthe polyformaldehyde; and (3) a medical device comprising a flexiblesealed polymeric dispenser that is preferably made of a polyolefin, suchas polyethylene and polypropylene containing a cyanoacrylate-basedtissue adhesive. It is preferred that the cyanoacrylate-based tissueadhesive comprising methoxypropyl cyanoacrylate contained in a sealedtapered flexible tube made of polyethylene or polypropylene. It is alsopreferred that the sealed laminated foil pack is further comprising aformaldehyde reactive nitrogenous compound, capable of reacting withgaseous formaldehyde, selected from the group represented by urea andmelamine encased and retained in a sealed non-woven polyolefin or wovenpolyethylene terephthalate porous pouch.

A key aspect of this invention deals with a hermetically sealedlaminated foil pack for use in radiochemical sterilization of at leastone medical device wherein the medical device comprises a flexiblesealed polymeric dispenser containing a cyanoacrylate-based tissueadhesive. The sealed pack also comprises unstabilized microparticulatesof radiolytically depolymerizable polyformaldehyde encased and retainedin a sealed non-woven polyolefin or a woven polyethylene terephthalateporous pouch.

For those embodiments of the present invention which employ a perforatedfolder for holding a medical device, a preferred folder is illustratedat FIGS. 1-5. FIG. 1 shows the preformed folder in its open, unfoldedconfiguration. Base wall 12 includes numerous perforations 14 definedtherein. Also defined in base wall 12 are U-shaped grooves 16 and 16′.These grooves define tabs 18 and 18′ for holding a medical device suchas a length of suture. The outer perimeter of the base wall 12 isdefined by preformed creases 20, 22, 24, and 26. Side walls 28 and 30extend outwardly from creases 22 and 24, respectively. Top wall 32extends outwardly from crease 20, includes numerous perforations 14, andfurther defines flap 34. Top wall 36 extends outwardly from crease 26,includes numerous perforations 14, and notch 38 defined therein. FIG. 2shows the folder as the side and top walls are being folded. As isbetter shown in FIGS. 3 and 4, side walls 28 and 30 are folded in towardthe base wall 12 first. Then, top wall 36 is folded over the side wallsand, finally, top wall 32 is folded over top wall 36. To secure thefolder in its closed position flap 34 is inserted into notch 38. Thus,when the folder is closed, the perforations defined in the top walls andthe base wall allow for the free flow of a desired gas around thecontained medical device. As noted above, while the perforated folder ofthe present invention must be sufficiently stiff to hold the medicaldevice in place and fold into its closed configuration, it may be formedof any suitable material, although cellulosic or polyolefinic materialsare preferred.

Additional illustrative examples associated with this invention areoutlined below:

Example 1 Radiochemical Sterilization of Polyglycolide (PG) BraidedSutures

A number of vacuum dried 27 inch lengths of size 2-0 braided sutureswere individually placed in a predried, perforated paper folder asdescribed in FIG. 1 and placed in four groups of 3″×5″ laminated foilpacks having a sealed, non-woven polyethylene (Tyvek®) porous pouchfilled with microparticulates of unstabilized Celcon® M-90polyformaldehyde (200 mg). The first group (I) contained thesuture/folder and the Celcon pouch. Into the second group (II) of packswas placed a second sealed, non-woven Tyvek® pouch containing drymelamine microparticulate (20 mg). In the third group (III) of packs wasplaced a sealed, non-woven Tyvek® pouch containing dry microparticulateurea (20 mg). In the fourth group (IV) of packs was placed a spore striphaving a spore count of 10⁷. Groups I to IV were prepurged twice withdry nitrogen and hermetically sealed. The sealed packs were gammairradiated with about 5 kGy using a Co-60 source at a dose rate of 32kGy/hr. Two weeks after the irradiation, the packs ere divided intoseparate groups and tested using standard techniques needed to determine(1) the residual formaldehyde in the package; (2) suture sterility; (3)reduction in spore count in the spore strip; and/or (4) retention of thesuture tensile properties. An outline of the experimental design andsummary of results are shown in Table I.

TABLE I Outline of the Experimental Design and Results ofRadiochemically Sterilized PG Braided Size 2-0 Sutures Average Resultsfor Experiment Group I Group II Group III Group IV Residual formaldehyde<10  <2  <2 <10 package, μg Suture sterility, % 100 100 100 100 Logreduction in spore — — —   7 count in spore strip Suture breakingstrength >95 >97 >97 >97 retention, %

Example 2 Radiochemical Sterilization of Absorbable Cyanoacrylate-BasedTissue Adhesive Formulation

Two types of methoxypropyl cyanoacrylate(MPC)-based tissue adhesiveformulations, A and B, were packaged under nitrogen atmosphere in sealedpolyethylene dispensers (volume=1 mL) with tapered necks. Each dispensercontained 0.4 mL of liquid formulation. Formulation A contained MPC, anabsorbable polyester modifier and a trace amount of stabilizer toprotect the formulation against premature anionic polymerization. Informulation B, the cyanoacrylate monomer consisted of a mixture of MPCand ethyl cyanoacrylate. Pairs of the dispensers containing formulationA or B were placed in groups of 3″×5″ laminated foil packs, eachcontaining a sealed non-woven polyethylene (Tyvek®) porous pouch filledwith microparticulate of unstabilized Celcon® M-90 polyformaldehyde (200mg). The first group (I-A and I-B for formulations A and B,respectively) contained the pairs of formulation A or B dispensers andthe Celcon® pouch. Into the second group (II-A and II-B) of the packswas placed a second sealed, non-woven Tyvek® pouch containing drymelamine microparticulate (20 mg). In the third group (III-A and III-B)of packs was placed a sealed non-woven Tyvek® pouch containing drymicroparticulate urea (20 mg). In the fourth group of packs (IV-A andIV-B) was placed a spore strip having a spore count of 10⁷. Groups I-Ato IV-A and I-B to IV-B were purged with dry nitrogen and hermeticallysealed. The sealed packs were gamma irradiated with about 5 kGy using aCo-60 source at a dose rate of 32 kGy/hr. Two weeks after irradiation,the packs were divided into separate groups and tested using standardtechniques needed to determine (1) the residual formaldehyde in thepackage; (2) sterility of the liquid formulation and the outside surfaceof the polyethylene dispenser; (3) the reduction in spore count in thespore strip; and/or (4) retention of the tissue adhesive properties. Anoutline of the experimental design and summary of results are shown inTable II.

TABLE II Outline of the Experimental Design and Results ofRadiochemically Sterilized Cyanoacrylate-based Tissue AdhesiveFormulations Average Results for Formulation Average Results forFormulation A Group B Group I-A II-A III-A IV-A I-B II-B III-B IV-BResidual formalde- 10 <2 <2 <10 <10 <2 <2 <10 hyde, μg Liquid adhesive  

———————————— 100 ————————————

Sterility, % Dispenser surface

———————————— 100 ————————————

sterility, % Log reduction in — — — 7 — — — 7 spore count in spore stripIncrease in formula-

———————————— <40 ————————————

tion viscosity, % Decrease in formula-

———————————— <10 ————————————

tion adhesive joint strength, %

Although the present invention has been described in connection with thepreferred embodiments, it is to be understood that modifications andvariations may be utilized without departing from the principles andscope of the invention, as those skilled in the art will readilyunderstand. Accordingly, such modifications may be practiced within thescope of the following claims. Moreover, Applicants hereby disclose allsubranges of all ranges disclosed herein. These subranges are alsouseful in carrying out the present invention.

1. A hermetically sealed package for use in radiochemical sterilizationof at least one medical device contained therein comprising: anessentially gas impervious, moisture impervious sealed outer sheet; aperforated folder contained within the sealed outer sheet for holdingthe medical device; a first sealed porous pouch contained within thesealed outer sheet and containing a radiolytically depolymerizablepolyformaldehyde microparticulate; and a second sealed porous pouchcontained within the sealed outer sheet and containing aformaldehyde-reactive microparticulate compound.
 2. A hermeticallysealed package as set forth in claim 1 wherein the outer sheet comprisesa laminated foil.
 3. A hermetically sealed package as set forth in claim1 wherein the perforated folder comprises a dried cellulosic material.4. A hermetically sealed package as set forth in claim 1 wherein theperforated folder comprises a polyolefinic material.
 5. A hermeticallysealed package as set forth in claim 4 wherein the perforated foldercomprises polyethylene.
 6. A hermetically sealed package as set forth inclaim 1 wherein the radiolytically depolymerizable polyformaldehydemicroparticulate comprises unstabilized polyformaldehyde.
 7. Ahermetically sealed package as set forth in claim 1 wherein theformaldehyde-reactive microparticulate compound comprises a reactivenitrogenous compound capable of reacting with gaseous formaldehydeselected from the group consisting of urea and melamine.
 8. Ahermetically sealed package as set forth in claim 1 wherein at least oneof the first and second sealed porous pouches comprises a non-wovenfabric construct comprising a polyolefinic material selected from thegroup consisting of polyethylene, polypropylene, and ethylene/propylenecopolymer.
 9. A hermetically sealed package as set forth in claim 1wherein at least one of the first and second sealed porous pouchescomprises a woven fabric construct comprising polyethyleneterephthalate.
 10. A hermetically sealed package as set forth in claim 1wherein the medical device comprises an absorbable suture braid.
 11. Ahermetically sealed package as set forth in claim 1 wherein the medicaldevice comprises an absorbable monofilament suture.
 12. A hermeticallysealed package as set forth in claim 1 wherein the medical devicecomprises an absorbable mesh.
 13. A hermetically sealed package as setforth in claim 1 wherein the medical device comprises a partiallyabsorbable vascular graft.
 14. A hermetically sealed package as setforth in claim 1 wherein the medical device comprises an absorbabledevice for internal bone fixation.
 15. A hermetically sealed package asset forth in claim 1 wherein the medical device comprises an absorbablestent.
 16. A hermetically sealed package as set forth in claim 1 whereinthe device is a metallic stent covered with an absorbable fibrousconstruct.
 17. A hermetically sealed package as set forth in claim 1wherein the medical device is a vascular repair device comprising atleast one absorbable component.
 18. A hermetically sealed package as setforth in claim 1 wherein the medical device is formed of polypropylene.19. A hermetically sealed package as set forth in claim 1 wherein atleast one of the first and second sealed porous pouches comprises awoven fabric construct comprising polyethylene terephthalate.
 20. Ahermetically sealed package for use in radiochemical sterilization of atleast one medical device comprising: an essentially gas impervious,moisture impervious sealed outer sheet; a medical device containedwithin the sealed outer sheet; a first sealed porous pouch containedwithin the sealed outer sheet and containing a radiolyticallydepolymerizable polyformaldehyde microparticulate; and a second sealedporous pouch contained within the sealed outer sheet and containing aformaldehyde-reactive microparticulate compound.
 21. A hermeticallysealed package as set forth in claim 20 wherein the outer sheetcomprises a laminated foil.
 22. A hermetically sealed package as setforth in claim 20 wherein the medical device comprises a flexible sealedpolymeric dispenser containing a cyanoacrylate-based tissue adhesive.23. A hermetically sealed package as set forth in claim 22 wherein thecyanoacrylate-based tissue adhesive comprises methoxypropylcyanoacrylate and wherein the flexible sealed polymeric dispensercomprises a polyolefin selected from polyethylene and polypropylene. 24.A hermetically sealed package as set forth in claim 20 wherein theradiolytically depolymerizable polyformaldehyde microparticulatecomprises unstabilized polyformaldehyde.
 25. A hermetically sealedpackage as set forth in claim 20 wherein the formaldehyde-reactivemicroparticulate compound comprises a reactive nitrogenous compoundcapable of reacting with gaseous formaldehyde selected from the groupconsisting of urea and melamine.
 26. A hermetically sealed package asset forth in claim 20 wherein at least one of the first and secondsealed porous pouches comprises a non-woven fabric construct comprisinga polyolefinic material selected from the group consisting ofpolyethylene, polypropylene, and ethylene/propylene copolymer.